Viscosine as a Potent and Safe Antipyretic Agent Evaluated by Yeast-Induced Pyrexia Model and Molecular Docking Studies.

The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure-activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy -17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E2 in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.

Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships.

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., ß-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 µM), superoxide (28.18 ± 1.35% inhibition at 100 µM) and CUPRAC (A0.5: 35.89 ± 0.09 µM) assays. Compound 5 (IC50: 11.02 ± 0.02 µM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 µM) in ß-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 µM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.

Antioxidant, anticholinesterase and tyrosinase inhibition activities, and fatty acids of Crocus mathewii - A forgotten endemic angiosperm of Turkey.

Context We report the first ever chemical/biochemical study on Crocus mathewii Kerndorff (Iridaceae) - a Turkish endemic angiosperm. This plant has never been explored for its phytochemistry and bioactivities. Objective This study explores C. mathewii corm and aerial parts for the chemical and biological properties of hexane, ethyl acetate, methanol and water fractions of the extracts. Material and methods Plant material (20 g) was extracted by methanol (250 mL × 5, 3 days each) and fractioned into hexane, ethyl acetate, methanol and water. All fractions were subjected to ß-carotene-linoleic acid, DPPH(·), ABTS(·)(+), CUPRAC, metal chelating and tyrosinase inhibition activities. Hexane fractions were submitted to GC-MS analysis. Results Ethyl acetate fractions showed excellent IC50 values in DPPH(·) (aerial 36.21 ± 0.76 and corm 33.87 ± 0.02 mg/L) and ABTS(·)(+) (aerial 33.01 ± 0.79 and bulb 27.87 ± 0.33 mg/L); higher than the IC50 of the standard α-tocopherol (DPPH 116.25 ± 1.97; ABTS 52.64 ± 0.37 mg/L), higher than BHA in DPPH (57.31 ± 0.25 mg/L), but slightly lower in ABTS (19.86 ± 2.73 mg/L). Methanol extract of aerial parts also showed higher activity than α-tocopherol in DPPH (85.56 ± 11.51 mg/L) but slightly less (72.90 ± 3.66 mg/L) than both the standards in ABTS. Linoleic (aerial 53.9%, corm 43.9%) and palmitic (aerial 22.2%, corm 18%) were found as the major fatty acids. Discussion and conclusion Some fractions of C. mathewii showed higher antioxidant activities than the standards. There is a need to explore more about this plant.

Hautriwaic acid as one of the hepatoprotective constituent of Dodonaea viscosa.

It is widely known that hepatitis and its complications such as cirrhosis or hepatocellular carcinoma are one of the major health problems of the world especially since no specific treatment is available. In the present study we investigated the hepatoprotective potential of the methanolic extract of the whole plant of Dodonaea viscosa and its ethyl acetate, aqueous, butanol and n-hexane fractions against carbon tetrachloride (CCl4) induced hepatoxicity in rats. Hepatoprotection was assessed in terms of reduction in serum enzymes (ALT, AST, and ALP) that occur after CCl4 injury, and by histopathology and immunohistochemistry. The methanolic extract reduced the serum enzyme level (ALT, AST, and ALP) down to control levels despite CCl4 treatment. It also reduced the CCl4-induced damaged area to 0% as assessed by histopathology. The CD68+ macrophages were also reduced in number around the central vein area by the methanolic extract. These hepatoprotective effects were better than the positive control silymarin. Similar hepatoprotective activities were found with the ethyl acetate, and aqueous fractions of the methanolic extract. The butanol and n-hexane fractions showed elevated levels of ALT, AST and ALP as compared to the positive control silymarin. Histopathology showed ∼30% damage to the liver cells with the butanol and n-hexane fractions which still showed some protective activity compared to the CCl4 treated control. HPLC fingerprinting suggested that hautriwaic acid present in the methanolic extract and its ethyl acetate, and aqueous fractions may be responsible for this hepatoprotective activity of Dodonaea viscosa which was confirmed by in vivo experiments.

Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens.

The main aim of the current study was to explore molecular insights for potentially new dual cholinesterase inhibitor(s) from Asparagus adscendens via molecular docking. This medicinal plant is traditionally used as a nerve tonic and remedy for memory impairments. Conypododiol was isolated from the chloroform fraction of methanolic extract of A. adscendens, based on bioactivity guided isolation. Conypododiol exhibited significant inhibition of both acetylcholinesterase and butyrylcholinesterase, having the IC(50) values 2.17 ± 0.1 µM and 11.21 ± 0.1 µM, respectively. IC(50) values of the standard compound Galanthamine for both the enzymes were 0.537 ± 0.018 µM and 8.6 ± 0.27 µM, respectively. Based on MTT cytotoxicity assay, Conypododiol was found safe against LCMK-2 monkey kidney epithelial cells and mice hepatocytes. Molecular docking studies revealed the hydrogen bonding interactions of Conypododiol with His440 and Ser200 at esteratic site (ES), and also with Tyr334 at peripheral anionic site (PAS) of the aromatic gorge of acetylcholinesterase. Simultaneous contacts of Conypododiol with PAS and ES shows its significance as a bivalent ligand. This preliminary study highlighted the potential of Conypododiol to be further developed and modified as new lead compound identified by its folk use.

Anti-inflammatory activities of Sieboldogenin from Smilax china Linn.: experimental and computational studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china Linn. is extensively used in traditional Chinese medicine (TCM) as well as in Pakistan for several medicinal purposes including their use in inflammatory disorders. AIM OF THE STUDY: The aims of the current study were to validate and assess the folk use of Smilax china Linn. on pharmacological grounds using the isolated compound at molecular, in vivo and computational levels. MATERIALS AND METHODS: Seiboldogenin was isolated from ethyl acetate fraction of the plant crude extract. In vitro lipoxygenase and in vivo carrageenan-induced hind paw oedema models were used in experimental studies while molecular docking technique was used to conduct computational study. RESULTS: Sieboldogenin showed significant lipoxygenase inhibition (IC50: 38 microM). It also exhibited significant inhibition (p<0.05) of carrageenan-induced hind paw oedema at the doses of 10 and 50mg/kg. Computational molecular docking showed its molecular interaction with important amino acid residues in the catalytic site of lipoxygenase, revealing its potential binding mode at molecular level. CONCLUSIONS: Sieboldogenin seems to be a potential new anti-inflammatory compound responsible for anti-inflammatory activities of Smilax china Linn. Its in vitro and in vivo inflammatory activities are in good agreement with the folk medicinal use of Smilax china Linn. in inflammatory disorders.